tbuckley/cabot-search huggingface dataset:
Risk Assessment for Neurobehavioral Toxicity
Authors: Donald E. McMillan
Journal: Environmental Health Perspectives (1987)

A study by the National Academy of Sciences/National Research Council (NAS/NRC) found neurobehavioral toxicity to be one of the areas where almost no data are available for the assessment of toxicity. Using the NAS/NRC report and a data base from the American Conference of Government Industrial Hygienists (ACGIH), an estimate of the number of neurobehavioral toxins in commercial chemicals can be made. Although the assumption made in making such a calculation may be invalid, the exercise suggests that the number of neurobehavioral toxins may be quite large. There does seem to be general agreement as to what type of neurobehavioral test procedures are appropriate for regulatory purposes. Select committees have consistently recommended the use of test batteries that include schedule-controlled behavior, motor activity, and neuropathological examination following in vivo perfusion, for regulatory purposes. Alkyltin data developed from such a battery were applied to the risk assessment model employed by the United States Environmental Protection Agency (EPA) in their calculations of acceptable daily intake. Using this test battery and the EPA risk assessment model, the acceptable daily intake calculated is of the same order of magnitude as the total limit values established by the ACGIH. A number of special issues in neurobehavioral toxicity also are discussed, including the definition of adverse neurobehavioral toxic effects, species extrapolation, correlation of behavior and neuropathology, alternative methods, and quality of life issues.
Abstract 13448: Impact of Diabetes on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study
Authors: Hiromichi Wada, Takashi Unoki, masahiro suzuki, Morihiro Matsuda, Yoichi Ajiro, Tsuyoshi Shinozaki, Satoru Sakagami, Kazuya Yonezawa, masatoshi shimizu, JUNICHI FUNADA, Takashi Takenaka, Yukiko Morita, Toshihiro Nakamura, Kazuteru Fujimoto, Hiromi Matsubara, Toru Kato, Daisuke Takagi, Kyohma Wada, Miyaka Wada, Moritake Iguchi, Nobutoyo Masunaga, MITSURU ISHII, Kazuhiko Kotani, Mitsuru Abe, Masaharu Akao, Koji Hasegawa
Journal: Circulation (2020)

Background: Diabetes mellitus (DM) is still significantly associated with the risk of mortality in the general population. Higher circulating growth differentiation factor 15 (GDF-15) levels are associated with the risk of mortality in the general population, in patients with DM, and in those with coronary artery disease (CAD). However, whether GDF-15 levels differ according to the diabetic status and whether DM modifies the relationship between GDF-15 and mortality in patients with stable CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between diabetic status and GDF-15 and the impact of DM on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 797 DM and 663 non-DM patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with DM exhibited significantly higher levels of GDF-15 compared to those without DM (median [interquartile range], 1472 [1049-2258] vs. 1274 [868-1874] pg/mL, respectively; P &lt;0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, DM, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P &lt;0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI], 1.33-1.71). This association was still significant in patients with DM (HR, 1.52; 95% CI, 1.30-1.79) and in those without DM (HR, 1.57; 95% CI, 1.25-1.96). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with DM, but not in those without DM. Conclusions: Higher levels of GDF-15 were independently associated with DM in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with DM.
Letter: Pseudopatients.
Authors: H S Barrows
Journal: BMJ (1975)

<h3>Abstract</h3> Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in the <i>d</i><sub><i>N</i></sub>/<i>d</i><sub><i>S</i></sub> ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively.
Tremelimumab: A monoclonal antibody against CTLA-4—In combination with subtotal ablation (trans catheter arterial chemoembolization (TACE), radiofrequency ablation (RFA) or cryoablation) in patients with hepatocellular carcinoma (HCC) and biliary tract carcinoma (BTC).
Authors: Austin G. Duffy, Oxana V. Makarova-Rusher, Drew Pratt, David E Kleiner, Susanna Ulahannan, Donna Mabry, Suzanne Fioravanti, Melissa Walker, Stephanie Carey, William Douglas Figg, Seth M. Steinberg, Victoria Anderson, Elliot Levy, Venkatesh Krishnasamy, Bradford J. Wood, Tim F. Greten
Journal: Journal of Clinical Oncology (2016)

4073 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. Transcatheter arterial chemoembolization (TACE), radiofrequency (RFA) and cryoablation (CA) have been shown to induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment. Methods: Patients with HCC [Childs Pugh A/B7; BCLC B/C; ECOG 0/1; post-sorafenib (BCLC stage C only)] or refractory BTC were enrolled in a study of Tremelimumab combined with subtotal TACE, RFA or CA performed on week 6. All BTC patients received RFA in combination with tremelimumab. Tumor biopsies were performed at baseline and at time of RF/TACE. Results: 41 pts enrolled (32 HCC, 9 BTC). Characteristics: M:F 31:10; Median age 54(range 42-76); In HCC pts cirrhosis present in 22pts, BCLC Stage B/C: 9/23; Hepatitis B/C/neg: 5/18/9. 14 pts received TACE, 19 underwent RFA (inc all 9 BTC pts), 5 CA during week 6 of tremelimumab therapy. 3 pts did not receive an ablative procedure (due to PD). No DLT encountered. Most common toxicity was pruritus. Of N = 17 pts evaluable for response outside of TACE/RFA-treated lesion 4 (23.5%) achieved confirmed partial responses. 10 of 12 pts with quantifiable HCV experienced a marked reduction in viral load. 6-week tumor biopsies showed clear increase in CD8+ T cells only in pts showing a clinical response. Flow cytometry of PBMC revealed statistically significant changes in CD4/Treg and CD8/Treg ratio only in patients showing clinical response. Median PFS for evaluable HCC population was 5.7m. Conclusions: Tremelimumab in combination with subtotal TACE, RFA or CA in patients with advanced HCC and BTC is safe and leads to the accumulation of intratumoral CD8+ T cells, activation of CD4+ and CD8+ T cells in peripheral blood in responding patients. Encouraging clinical activity seen with objective confirmed responses, PFS 5.7m and possibly surrogate reductions in HCV viral load. Clinical trial information: NCT01853618.
Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study
Authors: Sofia Ramiro, Rémy L M Mostard, César Magro-Checa, Christel M P van Dongen, Tom Dormans, Jacqueline Buijs, Michiel Gronenschild, Martijn D de Kruif, Eric H J van Haren, Tom van Kraaij, Mathie P G Leers, Ralph Peeters, Dennis R Wong, Robert B M Landewé
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only. Methods From 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein &gt;100 mg/L; ferritin &gt;900 µg/L; D-dimer &gt;1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2–5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation. Results At baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses. Conclusions A strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.
The Public Service
Journal: JAMA (1899)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Oldest case of sarcoidosis in the world.
Journal: BMJ (1981)

and the astute pathologist (I)r D Eakins) noted that the lymph node attached to the gall bladder showcd classical sarcoid.When she Xwas admitted on that occasion hcr x-ray film showed infiltrative changes and her EGG showed first-degree heart block xwith dropped beats and left bundle-branch block.''hus there was definite active sarcoidosis at the age of 88 years, though not actually "acute sarcoidosis" as rcported by Dr Brown and his colleagues.
Lipoma of the colon
Authors: B. S. Wolf
Journal: JAMA (1976)

IT IS NOT generally realized that the diagnosis of lipoma of the colon can often be made with considerable confidence by barium enema examination.<sup>1,2</sup>This is of practical importance since these tumors are benign and never become malignant. They are encapsulated, and, if operated on, can usually be removed through a simple colotomy or by myotomy and enucleation without entering the lumen of the bowel. Ninety percent of lipomas originate in the submucosa and grow slowly over a period of years without producing any symptoms.<sup>3</sup>They are commonly identified in older individuals, are usually single, greater than 3 cm in diameter, and involve the right side of the colon more often than the left. Due to motor activity of the colon and contraction of the muscularis propria deep to the tumor, there is a progressive tendency for extrusion of the submucosal mass into the lumen of the bowel.
SPASMODIC DIPLOPIA
Authors: GEORGE H. HYSLOP
Journal: JAMA (1924)

Double vision, either transitory or constant, is a fairly common symptom in the practice of ophthalmology and neurology. During the last five years, the literature of epidemic encephalitis has so emphasized diplopia as being a symptom of diagnostic importance that perhaps one is apt to regard it, in certain types of obscure cases, as evidence of encephalitis. Constant diplopia is not so difficult to account for in a given patient. It is my purpose in this paper to present a small series of cases in which transitory diplopia occurred and had a significance which, I believe, is worthy of discussion. In eliciting a history of this symptom, it is important to differentiate distinct double vision from mere blurring or indistinctness of objects. It is not uncommon to have a patient say that he sees double at times, yet on questioning it is manifest that the patient refers merely to indistinctness
Museum scholars to apply Holocaust experience to 1990s biomedical issues
Authors: A. A. Skolnick
Journal: JAMA (1992)

IN APRIL 1993, a major new museum will open near the National Mall in Washington, DC, just 400 yards from the Washington Monument. The museum will not be another grandiose display of nature's wonders or of human achievements. It will be instead a place for remembering and for studying one of humankind's darkest deeds. In 1980, a unanimous act of Congress established the United States Holocaust Memorial Council and mandated the creation of a living memorial to the millions of victims of Nazi genocide. In keeping with the project's motto—"For the dead and the living, we must bear witness"— the council chose to build a museum and study center "to illuminate the future from the darkness of the past." <h3>Physicians' Holocaust Behavior</h3> A significant area of study at the museum will be the behavior of physicians in Central Europe during the Holocaust and how this knowledge can be used to
Glyceryl trinitrate and angina.
Journal: BMJ (1969)

MEDCAJOURNALGlyceryl Trinitrate and Angina Organic nitrates were introduced for the treatment of angina more than 100 years ago and have held their position almost unchallenged until the advent of the drugs causing beta- adrenergic blockade.Many different nitrates in different formulations have been tried in clinical practice, but glyceryl trinitrate is the most effective and widely used.As nitrates are powerful vasodilators, it was for long assumed that they relieved angina by increasing the blood flow to areas of the myocardium supplied by stenosed coronary arteries.In animals with a normal heart glyceryl trinitrate caused a substantial increase in coronary blood flow, but studies in patients with coronary disease have been limited by the diffi- culty in making satisfactory measurements of coronary blood flow.In recent years measurements of coronary flow have been made in man by means of inert gases and radioactive tracers.None of these methods is entirely satisfactory and the results obtained are conflicting.R. Gorlin and his colleagues' found that glyceryl trinitrate increased coronary blood flow by 63 % in patients with a normal coronary vasculature but by only 16% in patients with coronary artery disease.L. Bernstein and his colleagues2 found that sublingual glyceryl trinitrate caused a decrease of 5% in coronary vascular resistance but no significant increase in coronary blood flow, because the mean aortic pressure fell by 20%.The same workers injected 0-1 to 0-2 mg. of glyceryl trinitrate directly into the coronary arteries and found that flow increased by 64% in those with minimal coronary artery disease and 38% in patients with severe disease.In contrast to the disagreement about the effects of sub- lingual glyceryl trinitrate on coronary blood flow there is agreement that the vasodilating action of the drug decreases both venous return and peripheral resistance.Hence it reduces the work of the left ventricle and the tension-time index by an average of 25-30%.1 2 Recently R. P. Carson and co-workers3 have measured the
Cardiovascular Pharmacology
Authors: Massimo Calabresi
Journal: JAMA (1978)

This volume presents a series of reviews, particularly of recent contributions, of most topics of cardiovascular pharmacology. Chapters 1 and 4 discuss the regulation of the circulation and of the autonomic and central nervous mechanisms involved. These contributions are readable and informative; perhaps more extensive data on CNS neurotransmitters, both stimulant and inhibitory, might have been included. Chapter 2 is a somewhat superficial presentation of renal anatomy and physiology; the pharmacology of diuretic agents is succinct, yet may be adequate as an introductory guide to the subject. Chapter 3 deals with the reninangiotensin system; chapter 5 is a brief but lucid and discriminating presentation of the cardiovascular effects of the prostaglandins. Unavoidably, in view of our limited definitive knowledge, much of the information is not conclusive. The rest of the book deals with specific clinical entities. Obviously the contributors are well informed on their subjects; in general, however, the introductory
THE REACTION OF DEFENSE.
Journal: JAMA (1899)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Evaluation of an influenza virus vaccine, bivalent (types A2 and B)
Journal: JAMA (1969)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Surgical, bacteriological, and biochemical management of "infection stones"
Authors: N. J. Nemoy
Journal: JAMA (1971)

In patients with "infection stones," urea-splitting bacteria reside within the stones, protected from the action of antimicrobial agents. To achieve complete eradication of residual macroscopic particles, surgical removal is followed by renal irrigation with a multivalent, buffered organic acid solution while a bacteriologically sterile urine is maintained. In 14 consecutive cases followed for an average of 34 months, stones have not recurred. Antibacterial therapy was stopped in all patients within two to four weeks of discharge following surgery; only one patient, a paraplegic with an indwelling catheter, has had a urinary tract infection.
Auscultatory Acumen
Authors: John Robboy
Journal: JAMA (1961)

<h3>To the Editor:—</h3> The article "Auscultatory Acumen in the General Medical Population," inThe Journal, Sept. 3, page 32, is entirely unrevealing. During the past 30 years I have had the opportunity to observe and to comment frequently on the fact that at rounds, when they were still held at the bedside, doctors differ considerably in localizing and recognizing heart sounds and murmurs. It is, therefore, evident that most of us would profit by extra training. The better showing by present-day senior students and diplomates is, of course, to be expected. There certainly must have been some progress in teaching at our medical schools during these past 30 years. It would be tragic, indeed, if the diplomate with 5 years of postgraduate work were unable to localize a murmur correctly The teaching in my days, and I speak from my own experience only, was absolutely abominable. It was through our